The addition of cisplatin to standard therapy with gemcitabine and nab-paclitaxel was associated with a median overall survival that “has not been seen in stage IV pancreatic cancer,” according to Gayle Jameson, MSN, ACNP-BC, Nurse Practitioner Investigator of Clinical Trials, HonorHealth Research Institute, Scottsdale, AZ, who reported the results from a phase 1b single-arm pilot study using the triplet at the 2017 Gastrointestinal Cancers Symposium.
The study showed that the use of the triplet therapy led to a median overall survival of 16.5 months, with 11 of the 25 patients enrolled still alive at the time of the data presentation.
In the Stand Up To Cancer trial, multiple interstitial copy number aberrations were counted in the tumor genomes of patients with metastatic pancreatic cancer, making DNA repair deficiencies likely. “These types of tumors are very sensitive to platinums. That was our rationale for adding cisplatin,” said Ms Jameson.
“It was a phase 1b study; we didn’t know the right dose of cisplatin, so we started at 25 mg/m2 and went up to 50 mg/m2, which was too toxic, and that’s how we came up with 25 mg/m2. It’s a very low dose of cisplatin. Adding that, we’ve seen a very impressive response rate,” she added.
Overall, 25 patients with stage IV adenocarcinoma of the pancreas who had not received previous chemotherapy for systemic disease were enrolled at 3 US sites. The patients received nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2, each infused over 30 minutes on days 1 and 8 of a 21-day cycle. The patients also received 25 mg/m2 of cisplatin infused over 60 minutes, which was escalated to 50 mg/m2, after the nab-paclitaxel infusion.
Twenty-four patients were evaluable. By RECIST 1.1, the overall response rate (ORR) was 71%, with 2 complete responses (8.3%), 15 partial responses (62.5%), and 4 patients with stable disease (16.7%). The 71% ORR is “exceptional in stage IV pancreas disease,” said Ms Jameson.
Of the 25 patients, 18 had a ≥30% reduction in tumor size from baseline, and 3 had resolution of measurable tumor by RECIST.
“People who were going to respond tended to respond rather quickly,” she said. “It’s most dramatic when you look at the CA19-9. For those patients who had an abnormal level of CA19-9 at baseline, although levels went up at first in a couple of patients, they plummeted very quickly. By 90 days, a majority of patients had a tremendous drop in CA19-9, and we know that this can correlate with overall survival.”
The median survival to date is 16.5 months, which has not been seen previously in patients with stage IV pancreatic cancer, she said. A total of 64% of the patients were alive at 12 months, 20% were alive at 24 months, and 4% were still alive at 36 months.
The most common drug-related grade ≥3 adverse events were thrombocytopenia (76%) with no serious bleeding events, anemia (32%), neutropenia (24%), infection (20%), and diarrhea (16%).
Pending tissue analysis may expose new insights into tumor response and treatment strategies, said Ms Jameson. A study examining the triplet therapy of cisplatin, gemcitabine, and nab-paclitaxel in the neoadjuvant setting is also planned.
